IS ALZHEIMER’S DISEASE DRUG DEVELOPMENT BROKEN? WHAT MUST BE IMPROVED

2014 ◽  
pp. 1-6
Author(s):  
P.-J. Ousset ◽  
J. Cummings ◽  
J. Delrieu ◽  
V. Legrand ◽  
N. Prins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Development ◽  
Drop Out ◽  
New Drugs ◽  
Trial Duration ◽  
Surrogate Outcomes ◽  
Technical Requirements ◽  
Number Of Patients

During the decade from 2002 to 2012, 99.6% of the 244 agents tested for efficacy in slowing the progression of Alzheimer’s’ disease (AD) failed to achieve their primary endpoints. At a CTAD symposium on November 14, 2013, in San Diego, USA, an international group of AD researchers met to discuss the evolution of trials over the past 10 years and proposed a number of changes intended to streamline and enhance the efficiency of clinical trials. Approximately 1,031 AD trials were conducted between 2000 and 2012. The number of patients per trial site tended to decrease over time necessitating a larger number of sites. The use of biomarkers for enrichment purposes, or as measures of target engagement or surrogate outcomes, results in higher screen failure and drop-out rates, adding to trial duration and/or costs. Present disease modifying AD trials ask for increasing logistical and technical requirements, necessitating the creation of highly specialized trial facilities and limiting the participation of smaller sites. Due to heavy administrative and regulatory task, only about 13% of the team's time is used for the essential recruitment. Proposals and perspectives: Strategies suggested to improve the efficiency of recruitment include establishing “ready to go cohorts” in advance of trials using biomarkers and clinical measures. Simplification and harmonization of administrative procedures, including harmonization of certification procedures, are urgently needed. Alternative approaches, such as using the Internet to screen volunteers for possible inclusion needs to be evaluated. The AD drug development enterprise from discovery through clinical trials requires re-examination and re-organization if new drugs are to be delivered to patients in a timely way.

scholarly journals NEW DRUGS IN CLINICAL TRIALS FOR TREATMENT OF ALZHEIMER'S DISEASE

2015 ◽  
Vol 16 (2) ◽  
Author(s):  
Evelise Fernandes PIETROVSKI ◽  
Dandiany Camily Kuczera SOFKA ◽  
Rafaela Franco CLAUDINO
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
New Drugs

A Doença de Alzheimer (DA) é um transtorno neurodegenerativo crônico e progressivo manifestado por deterioração da memória e perda das funções cognitivas. Há várias hipóteses sobre as causas: perda do neurotransmissor acetilcolina (ACh), o depósito de peptídeo beta-amiloide formando as placas senis, os emaranhados neurofibrilares contendo a proteína TAU, mecanismos genéticos e inflamatórios. A atual farmacoterapia objetiva tratar sinais e sintomas gerados pela neurodegeneração. Portanto, objetivou-se apresentar os tratamentos farmacológicos que estão sendo avaliados em testes clínicos, que possam agir de maneira preventiva evitando a neurodegeneração irreversível. Também avaliar as drogas atuais com relação a efetividade e segurança do paciente. Entre os novos medicamentos podem ser citados: a terapia antiamilóide; agonista de receptor GLP-1R (GLP-1R), que promove a inibição da formação das placas senis; antagonistas do receptor histaminérgico H3, para aumento na liberação de ACh; o bexarotene, impede o acúmulo do beta-amilóide; os inibidores da enzima conversora angiotensina (IECA); vitaminas do complexo B, reduzem os níveis de homocisteína; as estatinas e os anti-inflamatórios. Apesar de vários medicamentos estarem em testes clínicos o tratamento da DA ainda é um desafio, uma vez que não se sabe como se inicia, dificultando a reversão da neurodegeneração e, consequentemente, os sintomas decorrentes. 

scholarly journals New pharmacological strategies for the treatment of alzheimer’s disease

2021 ◽  
Author(s):  
Letícia Freitas de Castro Silva ◽  
Elisa Pinheiro Weber ◽  
Gleice Silva Toledo ◽  
Josiane Fonseca Almeida
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Tau Protein ◽  
Amyloid Β ◽  
The Elderly ◽  
New Drugs ◽  
Pathophysiological Mechanisms ◽  
Apoe Protein ◽  
New Biomarkers

Introduction: Alzheimer’s disease (AD) is seen as the most important dementia, prevalent in the elderly over 60 years old. There is still no cure, and the pharmacological strategies are to delay the symptoms and development of the pathology. The pathophysiological mechanisms are: hyperphosphorylation of the tau protein and aggregation of amyloid-β. Update studies of the tested therapies target the main pathological mechanisms: accumulation of β amyloid (inhibitors and modulators of β-secretase and γ-secretase and active and passive anti-Aβ immunotherapies), tau protein (inhibition of abnormal hyperphosphorylation with GSK-3 inhibitors, passive and active immunotherapies and the use of intrathecal antisense oligonucleotides (ASOs) and correction of the ApoE protein (increase lipidation, correct structure, clearance of non-lipid ApoE and reduction of ApoE expression). Objectives and methodology: To develop a bibliographic review in order to address new drugs in the treatment of Alzheimer’s. Qualitative and descriptive study carried out by literary review with research on PubMed. Results: Several drugs have been tested in clinical trials, however, due to lack of effectiveness, none have been approved. Therefore, it’s important to understand the limitations of the tests developed as flaws in the methodology, insufficient understanding of the mechanisms involved and inclusion of patients in different stages of AD, so that future investigations can overcome these gaps. Conclusion: It’s important to investigate new pathophysiological mechanisms, as well as the factors that trigger AD. Diagnosis is essential, with further studies to identify new biomarkers of the disease that will also have an impact on the conduct of clinical trials.

scholarly journals Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery

2020 ◽  
Vol 13 (11) ◽  
pp. 394 ◽  
Author(s):  
William M. Pardridge
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Blood Brain Barrier ◽  
New Drugs ◽  
Brain Barrier ◽  
Biologic Drugs ◽  
Blood Brain ◽  
Delivery Technology

Despite the enormity of the societal and health burdens caused by Alzheimer’s disease (AD), there have been no FDA approvals for new therapeutics for AD since 2003. This profound lack of progress in treatment of AD is due to dual problems, both related to the blood–brain barrier (BBB). First, 98% of small molecule drugs do not cross the BBB, and ~100% of biologic drugs do not cross the BBB, so BBB drug delivery technology is needed in AD drug development. Second, the pharmaceutical industry has not developed BBB drug delivery technology, which would enable industry to invent new therapeutics for AD that actually penetrate into brain parenchyma from blood. In 2020, less than 1% of all AD drug development projects use a BBB drug delivery technology. The pathogenesis of AD involves chronic neuro-inflammation, the progressive deposition of insoluble amyloid-beta or tau aggregates, and neural degeneration. New drugs that both attack these multiple sites in AD, and that have been coupled with BBB drug delivery technology, can lead to new and effective treatments of this serious disorder.

scholarly journals THE CASE FOR USING ACTIGRAPHY GENERATED SLEEP AND ACTIVITY ENDPOINTS IN ALZHEIMER’S DISEASE CLINICAL TRIALS

2016 ◽  
pp. 1-4
Author(s):  
M. Mc Carthy ◽  
W. Muehlhausen ◽  
P. Schüler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Development ◽  
Outcome Measures ◽  
Patient Population ◽  
Daily Activities ◽  
Site Staff ◽  
Consumer Devices ◽  
Relevant Outcome

More and more people in the industrialised world use wearables and smartphones to monitor their health and fitness. These devices are often used in combination with special apps to monitor and document daily activities and sleep. It would appear to be a logical step to assess the relevance of these devices in drug development trials. In contrast to the consumer devices, the technology used in clinical trials needs to be validated and compliant with the relevant regulations. Even under these complex requirements, wearables offer a number of new opportunities to objectively capture clinically relevant outcome measures –potentially with lower burden for patients and site staff. As an example, we describe the use in Alzheimer’s disease drug development studies. This is an indication where there have been a number of failures, in part due to the difficulties this patient population has in reliably completing existing tools. In addition rater scales add complexity due to inter- and intra-rater variability.

scholarly journals Mechanism-based treatments for Alzheimer's disease

2009 ◽  
Vol 11 (2) ◽  
pp. 159-169
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Inflammatory Response ◽  
Effective Treatment ◽  
Neurofibrillary Tangle ◽  
New Drugs ◽  
Amyloid Formation ◽  
Level Of Activity ◽  
High Level

Treatment for Alzheimer's disease is entering a new and exciting phase, with several new drugs beginning clinical trials. Many of these new therapies are based on our best current understanding of the pathogenesis of Alzheimer's disease, and are designed to try to either slow or halt the progression of the disease. There are several different theories underlying the current efforts, and these are briefly reviewed. Therapies directed against some aspect of beta-amyloid formation, against neurofibrillary tangle formation and against the inflammatory response are all considered, as are the problems associated with each area. It is as yet unclear which, if any, of these approaches will be successful, but the high level of activity in each of these three fields provides some hope that an effective treatment for Alzheimer's disease is on the horizon.

scholarly journals The PredictAD project: development of novel biomarkers and analysis software for early diagnosis of the Alzheimer's disease

2013 ◽  
Vol 3 (2) ◽  
pp. 20120072 ◽  
Author(s):  
Kari Antila ◽  
Jyrki Lötjönen ◽  
Lennart Thurfjell ◽  
Jarmo Laine ◽  
Marcello Massimini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Developed Countries ◽  
New Drugs ◽  
Brain Images ◽  
Age Related ◽  
Number Of Patients ◽  
Irreversible Effects ◽  
The Right

Alzheimer's disease (AD) is the most common cause of dementia affecting 36 million people worldwide. As the demographic transition in the developed countries progresses towards older population, the worsening ratio of workers per retirees and the growing number of patients with age-related illnesses such as AD will challenge the current healthcare systems and national economies. For these reasons AD has been identified as a health priority, and various methods for diagnosis and many candidates for therapies are under intense research. Even though there is currently no cure for AD, its effects can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data, electrophysiological measurements of the brain and structural, functional and molecular brain images. We also designed and built a statistical model and a framework for exploiting these biomarkers with other available patient history and background data. We were able to discover several potential novel biomarker candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials.

Alzheimer's disease: clinical trials and drug development

2010 ◽  
Vol 9 (7) ◽  
pp. 702-716 ◽  
Author(s):  
Francesca Mangialasche ◽  
Alina Solomon ◽  
Bengt Winblad ◽  
Patrizia Mecocci ◽  
Miia Kivipelto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Development
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